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Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin (DoRIS)

Primary Purpose

Hiv, Tuberculosis

Status
Recruiting
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Dolutegravir
Sponsored by
Helen Reynolds
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hiv

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ability to give informed consent prior to participation
  • Willing and able to comply with all study requirements
  • Receiving standard doses of RIF and INH
  • HIV antibody negative
  • Male or non-pregnant, non-breastfeeding female
  • Study participation will not extend length of ATT by more than 4 weeks

Exclusion Criteria:

  • < 18 years
  • Body weight < 50 kg
  • eGFR < 60 mL/min
  • Abnormal LFTs including ALT > 2.5 ULN
  • HIV antibody positive
  • Non-standard TB regimen (containing RHZE)
  • Women of childbearing age unless using effective contraception
  • Family history of sudden cardiac death
  • Prior history of cardiac disease that precludes the use of low dose digoxin
  • Medical or psychiatric condition that might affect participation in the study based on investigator judgement
  • Regular consumption of grapefruit or grapefruit juice
  • ECG abnormalities that preclude the use of low dose digoxin (intermittent complete heart block, second degree AV block, supraventricular arrhythmia associated with conducting pathways, ventricular tachycardia or fibrillation)

Sites / Locations

  • Desmond Tutu Health FoundationRecruiting
  • Infectious Diseases Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Dolutegravir

Arm Description

Outcomes

Primary Outcome Measures

Change in pharmacokinetic parameter Cmin of dolutegravir
Change in dolutegravir Cmin when dosed with standard, medium, high dose rifampicin

Secondary Outcome Measures

Change in pharmacokinetic parameter AUC of dolutegravir
Change in dolutegravir AUC when dosed with standard, medium, high dose rifampicin
Change in pharmacokinetic parameter Cmax of dolutegravir
Change in dolutegravir Cmax when dosed with standard, medium, high dose rifampicin
Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)
Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)

Full Information

First Posted
November 1, 2019
Last Updated
January 10, 2023
Sponsor
Helen Reynolds
Collaborators
Infectious Disease Institute, Kampala, Uganda, Desmond Tutu HIV Centre
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1. Study Identification

Unique Protocol Identification Number
NCT04166474
Brief Title
Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin
Acronym
DoRIS
Official Title
Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 18, 2021 (Actual)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Helen Reynolds
Collaborators
Infectious Disease Institute, Kampala, Uganda, Desmond Tutu HIV Centre

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a drug interaction study in HIV negative, TB-monoinfected participants coming to the end of continuation phase of TB therapy, to study the pharmacokinetic changes to dolutegravir when administered with standard, medium and high dose rifampicin.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hiv, Tuberculosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Dolutegravir
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Dolutegravir
Intervention Description
Dosed at 50 mg bd on 3 separate occasions with low, medium and high doses of rifampicin. Dosed at 50 mg od without rifampicin.
Primary Outcome Measure Information:
Title
Change in pharmacokinetic parameter Cmin of dolutegravir
Description
Change in dolutegravir Cmin when dosed with standard, medium, high dose rifampicin
Time Frame
Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Secondary Outcome Measure Information:
Title
Change in pharmacokinetic parameter AUC of dolutegravir
Description
Change in dolutegravir AUC when dosed with standard, medium, high dose rifampicin
Time Frame
Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Title
Change in pharmacokinetic parameter Cmax of dolutegravir
Description
Change in dolutegravir Cmax when dosed with standard, medium, high dose rifampicin
Time Frame
Day 14, Day 28, Day 42, 5 weeks post anti-tuberculosis treatment
Title
Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)
Description
Number of participants with Grade 3 and above adverse events as assessed by DAIDS (corrected v2.1 July 2017)
Time Frame
From first dose of dolutegravir until study completion approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ability to give informed consent prior to participation Willing and able to comply with all study requirements Receiving standard doses of RIF and INH HIV antibody negative Male or non-pregnant, non-breastfeeding female Study participation will not extend length of ATT by more than 4 weeks Exclusion Criteria: < 18 years Body weight < 50 kg eGFR < 60 mL/min Abnormal LFTs including ALT > 2.5 ULN HIV antibody positive Non-standard TB regimen (containing RHZE) Women of childbearing age unless using effective contraception Family history of sudden cardiac death Prior history of cardiac disease that precludes the use of low dose digoxin Medical or psychiatric condition that might affect participation in the study based on investigator judgement Regular consumption of grapefruit or grapefruit juice ECG abnormalities that preclude the use of low dose digoxin (intermittent complete heart block, second degree AV block, supraventricular arrhythmia associated with conducting pathways, ventricular tachycardia or fibrillation)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Helen Reynolds
Phone
+4401517945553
Email
her@liv.ac.uk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saye Khoo
Organizational Affiliation
University of Liverpool
Official's Role
Principal Investigator
Facility Information:
Facility Name
Desmond Tutu Health Foundation
City
Cape Town
Country
South Africa
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alicia James
First Name & Middle Initial & Last Name & Degree
Catherine Orrell
Facility Name
Infectious Diseases Institute
City
Kampala
Country
Uganda
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohammed Lamorde
Email
mlamorde@idi.co.ug

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Drug Interactions Between Dolutegravir and Escalating Doses of Rifampicin

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